Studies on the synthesis of the epidithiopiperazinedione ring system common to the gliotoxin-sporidesmin antibiotics are being pursued. An approach under investigation involved the use of unsaturated piperozinediones, i.e., 3,6-dimethylene-2,5- piperazinediones, as appropriate precursors for preparation of the epidithiopiperazinedione ring. Addition reactions that allow introduction of sulfur functions to the piperazinedione ring are under investigation. A second related approach involves the conversion of dehydroamino acids to alpha-mercaptoamino acids followed by oxidation to the disulfide and cyclization to the epidithiopiperazinedione.